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Dryad

Single cell RNA sequencing of human tissue along the stomach-intestinal tract

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Oct 30, 2024 version files 503.20 MB

Abstract

Enteroendocrine cells (EECs) are gut epithelial cells that respond to intestinal contents by secreting hormones, including incretins GLP-1 and GIP, which regulate multiple physiological processes. Hormone release is controlled through metabolite-sensing proteins. Low expression, interspecies differences, and existence of multiple EEC subtypes have posed challenges to the study of these sensors. We describe differentiation of stomach EECs to complement existing intestinal organoid protocols. CD200 emerged as a pan-EEC surface marker, allowing deep transcriptomic profiling from primary human tissue along the stomach-intestinal tract. We generated loss-of-function mutations in 22 receptors and subjected organoids to ligand-induced secretion experiments. We delineate the role of individual human EEC sensors in hormone secretion, including GLP-1. These represent potential pharmacological targets to influence appetite, bowel movement, insulin sensitivity and mucosal immunity.